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  • Title: Protective effect of pharmacologic preconditioning with pioglitazone on random-pattern skin flap in rat is mediated by nitric oxide system.
    Author: Afraz S, Kamran A, Moazzami K, Nezami BG, Dehpour AR.
    Journal: J Surg Res; 2012 Aug; 176(2):696-700. PubMed ID: 22137986.
    Abstract:
    BACKGROUND: Pioglitazone, a thiazolidinedione, is primarily used as an antidiabetic agent. In addition, recent reports have identified anti-ischemic and anti-inflammatory properties of pioglitazone through nitric oxide (NO) pathways. OBJECTIVE: To determine the protective effects of pioglitazone on random-pattern skin flaps in a rat model. METHODS: Forty-eight male Rats were randomly assigned to eight groups. Bipedicled dorsal skin flaps (2 × 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, three different doses of pioglitazone (25, 40, 80, mg/kg; doses were selected according to our pilot study) gavaged 4 h before elevating flaps. Seven days after operation, the survival of skin flap was measured. For investigating the role of NO system, in other groups the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg) was administered alone or with an effective dose of pioglitazone. Finally, in another group, subeffective dose of nitric oxide precursor L-arginine (100 mg/kg) was coadministered with subeffective pioglitazone. RESULTS: Significant increase in flap survival was seen with pioglitazone (40 mg/kg). This protective effect was abolished by systemic administration of L-NAME (10 mg/kg). Coadministration of subeffective doses of pioglitazone with subeffetcive L-arginine significantly improved flap survival. CONCLUSION: Pharmacologic preconditioning with pioglitazone improves survival of random-pattern skin flaps in rats through NO dependent mechanisms.
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